PROJECT SUMMARY The candidate for this K23 Patient-Oriented Research Career Development Award is a pediatric rheumatologist with training in clinical epidemiology and a research focus on neuropsychiatric disorders in pediatric systemic lupus erythematosus (pSLE). The typical onset of pSLE occurs at age 12-13 during the formative years of brain development and neural network maturation. This critical period may be disrupted by several disease-related factors including direct and indirect brain inflammatory effects, treatment, comorbid depression, anxiety, and chronic pain. However, there is a gap in our knowledge regarding the impact of pSLE on cognitive health and brain development. Enhanced characterization of age- and sex-expected trajectories of brain development is enabled through integration of multimodal neuroimaging techniques such as structural magnetic resonance imaging (sMRI), diffusion tensor imaging (DTI), and functional MRI (fMRI). Multimodal neuroimaging may elucidate mechanisms underlying effects of pSLE on the developing adolescent brain, with potential to critically impact neuropsychiatric and overall outcomes in pSLE. The proposed research innovatively applies optimized multimodal neuroimaging techniques to study trajectories of brain structure and function in pSLE, as well as contributing disease-related factors. Leveraging existing normative imaging, cognitive and psychiatric data from typically developing youth in the large Philadelphia Neurodevelopmental Cohort (n=1600), the proposed project will evaluate structural brain injury, and calculate newly developed measures of brain development. Aim 1 will quantify the effect of pSLE on age- and sex-expected brain structure, function, and development, comparing longitudinal multimodal neuroimaging (sMRI, DTI, and resting state fMRI) and cognitive metrics to normative data for age and sex-matched typically developing youth. Aim 2 will determine the relative contribution of disease-related factors to brain development and cognitive function in pSLE subjects. This proposal will develop the candidate?s: (1) expertise in assessment of cognitive health and brain development in pSLE; (2) skills for identification of potential intervention targets to optimize cognitive and behavioral health in pSLE. Guided by Primary Mentor Susan Furth, MD, PhD, an internationally-recognized clinical researcher with an outstanding record of mentorship, the candidate proposes a comprehensive interdisciplinary training program. She will receive expert mentorship from her Advisory Committee, as well as formal and informal training focused on her career development. The project will provide preliminary data for longitudinal studies examining biomarkers for early detection and targeted treatment of neuropsychiatric disorders in pSLE, towards the candidate?s long-term goal of improving outcomes in pSLE. This award will therefore provide a training platform to ensure the candidate?s success as an independent clinician investigator in pediatric rheumatology.